NM_021246.4:c.35C>G

Variant names:

• chr6-31715390-C-G
• rs1806344467
• NM_021246.4:c.35C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021246.4(LY6G6D):​c.35C>G​(p.Ser12Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LY6G6D NM_021246.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15
• Publications: 0 publications found

Genes affected

LY6G6D (HGNC:13935): (lymphocyte antigen 6 family member G6D) LY6G6D belongs to a cluster of leukocyte antigen-6 (LY6) genes located in the major histocompatibility complex (MHC) class III region on chromosome 6. Members of the LY6 superfamily typically contain 70 to 80 amino acids, including 8 to 10 cysteines. Most LY6 proteins are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that is directly involved in signal transduction (Mallya et al., 2002 [PubMed 12079290]).[supplied by OMIM, Apr 2009]

LY6G6F-LY6G6D (HGNC:38821): (LY6G6F-LY6G6D readthrough) This locus represents naturally occurring readthrough transcription between the neighboring LY6G6F (lymphocyte antigen 6 family member G6F) and LY6G6D (lymphocyte antigen 6 family member G6D) genes on chromosome 6. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21371037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY6G6D	NM_021246.4	MANE Select	c.35C>G	p.Ser12Cys	missense	Exon 1 of 3	NP_067069.2	A0A1L6Z9X4
	LY6G6F-LY6G6D	NM_001353334.2		c.803-112C>G		intron	N/A	NP_001340263.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY6G6D	ENST00000375825.8	TSL:1 MANE Select	c.35C>G	p.Ser12Cys	missense	Exon 1 of 3	ENSP00000364985.3	O95868
	LY6G6D	ENST00000375824.1	TSL:1	c.35C>G	p.Ser12Cys	missense	Exon 1 of 3	ENSP00000364984.1	F6XWZ1
	LY6G6F-LY6G6D	ENST00000503322.1	TSL:1	c.803-112C>G		intron	N/A	ENSP00000421232.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.072
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.32	N
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.2
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.089
Sift	Benign	0.066	T
Sift4G	Uncertain	0.028	D
Polyphen		0.88	P
Vest4		0.22
MutPred		0.33		Loss of stability (P = 0.0877)
MVP		0.36
MPC		0.39
ClinPred		0.37	T
GERP RS		4.3
PromoterAI		0.039	Neutral
Varity_R		0.11
gMVP		0.38
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1806344467; hg19: chr6-31683167;